Department of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
PLoS Negl Trop Dis. 2024 Feb 15;18(2):e0011929. doi: 10.1371/journal.pntd.0011929. eCollection 2024 Feb.
The drug praziquantel (PZQ) has served as the long-standing drug therapy for treatment of infections caused by parasitic flatworms. These encompass diseases caused by parasitic blood, lung, and liver flukes, as well as various tapeworm infections. Despite a history of clinical usage spanning over 4 decades, the parasite target of PZQ has long resisted identification. However, a flatworm transient receptor potential ion channel from the melastatin subfamily (TRPMPZQ) was recently identified as a target for PZQ action. Here, recent experimental progress interrogating TRPMPZQ is evaluated, encompassing biochemical, pharmacological, genetic, and comparative phylogenetic data that highlight the properties of this ion channel. Various lines of evidence that support TRPMPZQ being the therapeutic target of PZQ are presented, together with additional priorities for further research into the mechanism of action of this important clinical drug.
吡喹酮(PZQ)是一种久经考验的抗寄生虫药物,广泛用于治疗各种寄生虫感染,包括血液寄生虫、肺部寄生虫、肝脏寄生虫和各种绦虫感染。尽管该药物已在临床上使用了 40 多年,但 PZQ 的寄生虫靶点一直难以确定。然而,最近鉴定出一种来自 melastatin 亚家族的扁形动物瞬时受体电位离子通道(TRPMPZQ),被认为是 PZQ 的作用靶点。本文评估了最近关于 TRPMPZQ 的实验进展,包括生化、药理学、遗传学和比较系统发育学数据,这些数据突出了该离子通道的特性。本文还提出了支持 TRPMPZQ 是 PZQ 治疗靶点的各种证据,并提出了进一步研究该重要临床药物作用机制的额外优先事项。